The intermediate goal of the candidate, Kristina E. Howard, DVM, is to complete a mentored training program in retrovirus pathogenesis research, culminating in the PhD degree and providing the opportunity for continued postdoctoral study. Dr. Howard's long-term goal is to become a principal investigator employing animal models to investigate the mucosal immune pathogenesis of infectious diseases. The research training program will be conducted under the guidance of Dr. Gregg A. Dean and Dr. Wayne Tompkins, at North Carolina State University. The FlV research group, of which the co-sponsors are part, has a strong record of extramural funding and scientist training. The candidate's plan emphasizes laboratory training in the current molecular techniques and immunological research methods applied to an animal model of AIDS. This proposal employs the feline immunodeficiency virus (FIV) animal model in the testing of a novel oral vaccine strategy utilizing recombinant Listeria monocytogenes to express FIV proteins. The FIV/cat model is a well-established model of lentiviral immunodeficiency in a natural host that is characterized by the ability to initiate transmucosal infection utilizing either cell-associated or cell-free inoculum. Using a recombinant L. monocytogenes, we have recently shown that a single oral vaccination provided protection against vaginal FIV challenge. This proposal will characterize mucosal immunity conferred by this vaccine and assess potential mechanisms of protection. In the first aim we will assess mucosal and systemic immune responses following vaccination to better understand the specific responses induced by the vaccine. Aim 2 will assess the ability of the oral vaccine to protect against homologous versus heterologous mucosal FIV challenge and determine what specific humoral and cell-mediated immune responses may correlate with protection. Aim 3 addresses potential mechanisms by which this vaccine may protect the host from FIV infection. The results of these studies will provide establish whether or not this vaccine can protect against diverse FIV challenge, will identify mucosal immune responses that may be responsible for protection, and may identify additional immune system targets for enhanced vaccine development and therapeutic intervention.